Characterization of aggrephagy in exercise-induced muscle damage / 中国组织工程研究

ABSTRACT

BACKGROUND: A high-intensity eccentric exercise may lead to skeletal muscle damage, endoplasmic reticulum stress, increasing misfolded proteins. Aggrephagy works as an effective way of controlling quality of proteins and plays an important role in damage repair. OBJECTIVE: To discover the activation degree of aggrephagy in the damage repair process after an overload eccentric exercise, and to discuss the role of aggrephagy in the exercise-induced muscle damage, which is supplementary to the protein degradation pathway in skeletal muscle damage. METHODS: Sixty-four male adult Sprague Dawley rats were randomly divided into a static control group (n=8) and seven exercise groups according to post-exercise time (0, 3, 6,12, 24,48 and 72 hours, eight rats in each). Damage models were established by downhill running (-16°, 16 m/min, 90 minutes). Subsequently, the histological changes of the rat soleus muscle was observed under an electron microscope and protein expressions of histone deacetylase 6 and microtubule-associated protein 1 light chain 3II/I related to aggrephagy were detected using western bot assay. RESULTS AND CONCLUSION: (1) Under the transmission electron microscope, the rat soleus muscle was disordered and widened and appeared to have transient sarcomere, the Z line was water wave-like, broken and disappeared, and the mitochondria were swollen and unevenly distributed with an unclear structure after high-intensity eccentric exercise. The model rats suffered severest muscle damage at 12 hours and recovered completely at 72 hours after high-intensity eccentric exercise. (2) After one-time eccentric exercise, the expression of histone deacetylase 6 had a transient increase. The histone deacetylase 6 expression reached the peak at 6 hours, then gradually reduced and recovered at 72 hours after exercise. The microtubule-associated protein 1 light chain 3II/I expression was significantly increased at 3 hours after exercise, reached the peak at 12 hours, then reduced significantly and recovered at 72 hours after exercise. All these findings indicate that aggrephagy transiently happens and exerts important roles in the clearance of misfolded proteins, maintenance of cellular environmental homeostasis and recovery of skeletal muscle damage.